Download Physiology of Its Treatment Circulatory Shock and

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Circulatory Shock and
Physiology of Its Treatment
Circulatory shock means generalized inadequate
blood flow through the body, to the extent that the
body tissues are damaged because of too little flow,
especially because of too little oxygen and other
nutrients delivered to the tissue cells. Even the cardiovascular system itself—the heart musculature,
walls of the blood vessels, vasomotor system, and
other circulatory parts—begins to deteriorate, so
that the shock, once begun, is prone to become progressively worse.
Physiologic Causes of Shock
Circulatory Shock Caused by Decreased Cardiac Output
Shock usually results from inadequate cardiac output. Therefore, any condition
that reduces the cardiac output far below normal will likely lead to circulatory
shock. Two types of factors can severely reduce cardiac output:
1. Cardiac abnormalities that decrease the ability of the heart to pump blood.
These include especially myocardial infarction but also toxic states of
the heart, severe heart valve dysfunction, heart arrhythmias, and other
conditions. The circulatory shock that results from diminished cardiac
pumping ability is called cardiogenic shock. This is discussed in detail in
Chapter 22, where it is pointed out that as many as 85 per cent of people
who develop cardiogenic shock do not survive.
2. Factors that decrease venous return also decrease cardiac output because
the heart cannot pump blood that does not flow into it. The most common
cause of decreased venous return is diminished blood volume, but venous
return can also be reduced as a result of decreased vascular tone, especially
of the venous blood reservoirs, or obstruction to blood flow at some point
in the circulation, especially in the venous return pathway to the heart.
Circulatory Shock That Occurs Without Diminished
Cardiac Output
Occasionally, the cardiac output is normal or even greater than normal, yet the
person is in circulatory shock. This can result from (1) excessive metabolism of
the body, so that even a normal cardiac output is inadequate, or (2) abnormal
tissue perfusion patterns, so that most of the cardiac output is passing through
blood vessels besides those that supply the local tissues with nutrition.
The specific causes of shock are discussed later in the chapter. For the present,
it is important to note that all of them lead to inadequate delivery of nutrients
to critical tissues and critical organs and also cause inadequate removal of cellular waste products from the tissues.
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Chapter 24
279
Circulatory Shock and Physiology of Its Treatment
In the minds of many physicians, the arterial pressure
level is the principal measure of adequacy of circulatory function. However, the arterial pressure can often
be seriously misleading. At times, a person may be in
severe shock and still have an almost normal arterial
pressure because of powerful nervous reflexes that
keep the pressure from falling. At other times, the
arterial pressure can fall to half of normal, but the
person still has normal tissue perfusion and is not in
shock.
In most types of shock, especially shock caused by
severe blood loss, the arterial blood pressure decreases
at the same time as the cardiac output decreases,
although usually not as much.
Cardiac output and
arterial pressure
(percentage of normal)
What Happens to the Arterial Pressure
in Circulatory Shock?
Arterial
pressure
100
50
Cardiac
output
0
0
10
20
30
40
50
Percentage of total blood removed
Figure 24–1
Effect of hemorrhage on cardiac output and arterial pressure.
Tissue Deterioration Is the End Result
of Circulatory Shock, Whatever
the Cause
Once circulatory shock reaches a critical state of severity, regardless of its initiating cause, the shock itself
breeds more shock. That is, the inadequate blood flow
causes the body tissues to begin deteriorating, including the heart and circulatory system itself. This causes
an even greater decrease in cardiac output, and a
vicious circle ensues, with progressively increasing circulatory shock, less adequate tissue perfusion, more
shock, and so forth until death. It is with this late stage
of circulatory shock that we are especially concerned,
because appropriate physiologic treatment can often
reverse the rapid slide to death.
Stages of Shock
Because the characteristics of circulatory shock
change with different degrees of severity, shock is
divided into the following three major stages:
1. A nonprogressive stage (sometimes called
the compensated stage), in which the normal
circulatory compensatory mechanisms eventually
cause full recovery without help from outside
therapy.
2. A progressive stage, in which, without therapy,
the shock becomes steadily worse until death.
3. An irreversible stage, in which the shock has
progressed to such an extent that all forms of
known therapy are inadequate to save the
person’s life, even though, for the moment, the
person is still alive.
Now, let us discuss the stages of circulatory shock
caused by decreased blood volume, which illustrate the
basic principles. Then we can consider special characteristics of shock initiated by other causes.
Shock Caused by
Hypovolemia—Hemorrhagic
Shock
Hypovolemia means diminished blood volume. Hemorrhage is the most common cause of hypovolemic
shock. Hemorrhage decreases the filling pressure of the
circulation and, as a consequence, decreases venous
return. As a result, the cardiac output falls below
normal, and shock may ensue.
Relationship of Bleeding Volume to
Cardiac Output and Arterial Pressure
Figure 24–1 shows the approximate effects on both
cardiac output and arterial pressure of removing blood
from the circulatory system over a period of about 30
minutes. About 10 per cent of the total blood volume
can be removed with almost no effect on either arterial pressure or cardiac output, but greater blood loss
usually diminishes the cardiac output first and later the
arterial pressure, both of which fall to zero when about
35 to 45 per cent of the total blood volume has been
removed.
Sympathetic Reflex Compensations in Shock—Their Special
Value to Maintain Arterial Pressure. The decrease in arte-
rial pressure after hemorrhage—as well as decreases
in pressures in the pulmonary arteries and veins in the
thorax—causes powerful sympathetic reflexes (initiated mainly by the arterial baroreceptors and other
vascular stretch receptors, as explained in Chapter 18).
These reflexes stimulate the sympathetic vasoconstrictor system throughout the body, resulting in three
important effects: (1) The arterioles constrict in most
parts of the systemic circulation, thereby increasing
the total peripheral resistance. (2) The veins and
venous reservoirs constrict, thereby helping to maintain adequate venous return despite diminished blood
280
Arterial pressure
(percentage of control value)
Unit IV
The Circulation
I
100
90
80
70
60
50
40
30
20
10
0
II
III
IV
V
VI
0
60
120
180
240
300
Time in minutes
volume. (3) Heart activity increases markedly, sometimes increasing the heart rate from the normal value
of 72 beats/min to as high as 160 to 180 beats/min.
Value of the Sympathetic Nervous Reflexes. In the
absence of the sympathetic reflexes, only 15 to 20 per
cent of the blood volume can be removed over a
period of 30 minutes before a person dies; this is in
contrast to a 30 to 40 per cent loss of blood volume
that a person can sustain when the reflexes are intact.
Therefore, the reflexes extend the amount of blood
loss that can occur without causing death to about
twice that which is possible in their absence.
360
Figure 24–2
Time course of arterial pressure in dogs after different degrees of acute hemorrhage. Each curve
represents average results from six dogs.
The sympathetic stimulation does not cause significant
constriction of either the cerebral or the cardiac
vessels. In addition, in both these vascular beds, local
blood flow autoregulation is excellent, which prevents
moderate decreases in arterial pressure from significantly decreasing their blood flows. Therefore, blood
flow through the heart and brain is maintained essentially at normal levels as long as the arterial pressure
does not fall below about 70 mm Hg, despite the fact
that blood flow in some other areas of the body might
be decreased to as little as one third to one quarter
normal by this time because of vasoconstriction.
Greater Effect of the Sympathetic Nervous Reflexes in
Maintaining Arterial Pressure than in Maintaining
Cardiac Output. Referring again to Figure 24–1, note
Progressive and Nonprogressive
Hemorrhagic Shock
that the arterial pressure is maintained at or near
normal levels in the hemorrhaging person longer than
is the cardiac output. The reason for this is that the
sympathetic reflexes are geared more for maintaining
arterial pressure than for maintaining output. They
increase the arterial pressure mainly by increasing the
total peripheral resistance, which has no beneficial
effect on cardiac output; however, the sympathetic constriction of the veins is important to keep venous return
and cardiac output from falling too much, in addition
to their role in maintaining arterial pressure.
Especially interesting is the second plateau occurring at about 50 mm Hg in the arterial pressure curve
of Figure 24–1. This results from activation of the
central nervous system ischemic response, which
causes extreme stimulation of the sympathetic nervous
system when the brain begins to suffer from lack of
oxygen or from excess buildup of carbon dioxide, as
discussed in Chapter 18. This effect of the central
nervous system ischemic response can be called the
“last-ditch stand” of the sympathetic reflexes in their
attempt to keep the arterial pressure from falling too
low.
Figure 24–2 shows an experiment that we performed
in dogs to demonstrate the effects of different degrees
of sudden acute hemorrhage on the subsequent course
of arterial pressure. The dogs were bled rapidly until
their arterial pressures fell to different levels. Those
dogs whose pressures fell immediately to no lower
than 45 mm Hg (groups I, II, and III) all eventually
recovered; the recovery occurred rapidly if the pressure fell only slightly (group I) but occurred slowly if
it fell almost to the 45 mm Hg level (group III). When
the arterial pressure fell below 45 mm Hg (groups IV,
V, and VI), all the dogs died, although many of them
hovered between life and death for hours before the
circulatory system deteriorated to the stage of death.
This experiment demonstrates that the circulatory
system can recover as long as the degree of hemorrhage is no greater than a certain critical amount.
Crossing this critical threshold by even a few milliliters
of blood loss makes the eventual difference between
life and death. Thus, hemorrhage beyond a certain critical level causes shock to become progressive. That is,
the shock itself causes still more shock, and the condition becomes a vicious circle that eventually leads to
deterioration of the circulation and to death.
Protection of Coronary and Cerebral Blood Flow by
the Reflexes. A special value of the maintenance
Nonprogressive Shock—Compensated Shock
of normal arterial pressure even in the presence of
decreasing cardiac output is protection of blood flow
through the coronary and cerebral circulatory systems.
If shock is not severe enough to cause its own progression, the person eventually recovers. Therefore,
shock of this lesser degree is called nonprogressive
Chapter 24
Circulatory Shock and Physiology of Its Treatment
shock. It is also called compensated shock, meaning
that the sympathetic reflexes and other factors compensate enough to prevent further deterioration of the
circulation.
The factors that cause a person to recover from
moderate degrees of shock are all the negative feedback control mechanisms of the circulation that
attempt to return cardiac output and arterial pressure
back to normal levels. They include the following:
1. Baroreceptor reflexes, which elicit powerful
sympathetic stimulation of the circulation.
2. Central nervous system ischemic response,
which elicits even more powerful sympathetic
stimulation throughout the body but is not
activated significantly until the arterial pressure
falls below 50 mm Hg.
3. Reverse stress-relaxation of the circulatory system,
which causes the blood vessels to contract around
the diminished blood volume, so that the blood
volume that is available more adequately fills the
circulation.
4. Formation of angiotensin by the kidneys, which
constricts the peripheral arteries and also causes
decreased output of water and salt by the
kidneys, both of which help prevent progression
of shock.
5. Formation of vasopressin (antidiuretic hormone)
by the posterior pituitary gland, which constricts
the peripheral arteries and veins and greatly
increases water retention by the kidneys.
6. Compensatory mechanisms that return the blood
volume back toward normal, including absorption
of large quantities of fluid from the intestinal
tract, absorption of fluid into the blood capillaries
from the interstitial spaces of the body,
conservation of water and salt by the kidneys, and
increased thirst and increased appetite for salt,
which make the person drink water and eat salty
foods if able.
The sympathetic reflexes provide immediate help
toward bringing about recovery because they become
maximally activated within 30 seconds to a minute
after hemorrhage.
The angiotensin and vasopressin mechanisms, as
well as the reverse stress-relaxation that causes
contraction of the blood vessels and venous reservoirs,
all require 10 minutes to 1 hour to respond completely,
but they aid greatly in increasing the arterial pressure
or increasing the circulatory filling pressure and
thereby increasing the return of blood to the heart.
Finally, readjustment of blood volume by absorption
of fluid from the interstitial spaces and intestinal tract,
as well as oral ingestion and absorption of additional
quantities of water and salt, may require from 1 to 48
hours, but recovery eventually takes place, provided
the shock does not become severe enough to enter the
progressive stage.
“Progressive Shock” Is Caused by a Vicious
Circle of Cardiovascular Deterioration
Figure 24–3 shows some of the positive feedbacks that
further depress cardiac output in shock, thus causing
281
the shock to become progressive. Some of the more
important feedbacks are the following.
Cardiac Depression. When the arterial pressure falls low
enough, coronary blood flow decreases below that
required for adequate nutrition of the myocardium.
This weakens the heart muscle and thereby decreases
the cardiac output more. Thus, a positive feedback
cycle has developed, whereby the shock becomes more
and more severe.
Figure 24–4 shows cardiac output curves extrapolated to the human heart from experiments in dogs,
demonstrating progressive deterioration of the heart
at different times after the onset of shock. A dog was
bled until the arterial pressure fell to 30 mm Hg, and
the pressure was held at this level by further bleeding
or retransfusion of blood as required. Note from the
second curve in the figure that there was little deterioration of the heart during the first 2 hours, but by 4
hours, the heart had deteriorated about 40 per cent;
then, rapidly, during the last hour of the experiment
(after 4 hours of low coronary blood pressure), the
heart deteriorated completely.
Thus, one of the important features of progressive
shock, whether it is hemorrhagic in origin or caused in
another way, is eventual progressive deterioration of
the heart. In the early stages of shock, this plays very
little role in the condition of the person, partly because
deterioration of the heart is not severe during the first
hour or so of shock, but mainly because the heart has
tremendous reserve capability that normally allows
it to pump 300 to 400 per cent more blood than is
required by the body for adequate bodywide tissue
nutrition. In the latest stages of shock, however, deterioration of the heart is probably the most important
factor in the final lethal progression of the shock.
Vasomotor Failure. In the early stages of shock, various
circulatory reflexes cause intense activity of the
sympathetic nervous system. This, as discussed earlier,
helps delay depression of the cardiac output and
especially helps prevent decreased arterial pressure.
However, there comes a point when diminished blood
flow to the brain’s vasomotor center depresses the
center so much that it, too, becomes progressively less
active and finally totally inactive. For instance, complete circulatory arrest to the brain causes, during the
first 4 to 8 minutes, the most intense of all sympathetic
discharges, but by the end of 10 to 15 minutes, the vasomotor center becomes so depressed that no further
evidence of sympathetic discharge can be demonstrated. Fortunately, the vasomotor center usually does
not fail in the early stages of shock if the arterial
pressure remains above 30 mm Hg.
Blockage of Very Small Vessels—“Sludged Blood.” In time,
blockage occurs in many of the very small blood
vessels in the circulatory system, and this also causes
the shock to progress. The initiating cause of this
blockage is sluggish blood flow in the microvessels.
Because tissue metabolism continues despite the low
flow, large amounts of acid, both carbonic acid and
282
Unit IV
The Circulation
Decreased cardiac output
Decreased arterial pressure
Decreased systemic blood flow
Decreased cardiac nutrition
Decreased nutrition of tissues
Decreased nutrition of brain
Decreased nutrition
of vascular system
Intravascular clotting
Tissue ischemia
Decreased vasomotor
activity
Increased
capillary
permeability
Release of
toxins
Vascular dilation
Venous pooling
of blood
Cardiac depression
Decreased
blood volume
Decreased venous return
Figure 24–3
Different types of “positive feedback” that can lead to progression of shock.
lactic acid, continue to empty into the local blood
vessels and greatly increase the local acidity of the
blood. This acid, plus other deterioration products
from the ischemic tissues, causes local blood agglutination, resulting in minute blood clots, leading to very
small plugs in the small vessels. Even if the vessels do
not become plugged, an increased tendency for the
blood cells to stick to one another makes it more difficult for blood to flow through the microvasculature,
giving rise to the term sludged blood.
Increased Capillary Permeability. After many hours of
capillary hypoxia and lack of other nutrients, the
permeability of the capillaries gradually increases,
and large quantities of fluid begin to transude into the
tissues. This decreases the blood volume even more,
with a resultant further decrease in cardiac output,
making the shock still more severe. Capillary hypoxia
does not cause increased capillary permeability until
the late stages of prolonged shock.
Release of Toxins by Ischemic Tissue. Throughout the
history of research in the field of shock, it has been
suggested that shock causes tissues to release toxic
substances, such as histamine, serotonin, and tissue
enzymes, that cause further deterioration of the circulatory system. Quantitative studies have proved the
significance of at least one toxin, endotoxin, in some
types of shock.
Cardiac Depression Caused by Endotoxin. Endotoxin
is released from the bodies of dead gram-negative
bacteria in the intestines. Diminished blood flow to
the intestines often causes enhanced formation and
absorption of this toxic substance. The circulating
toxin then causes increased cellular metabolism
despite inadequate nutrition of the cells; this has a specific effect on the heart muscle, causing cardiac depression. Endotoxin can play a major role in some types
of shock, especially “septic shock,” discussed later in
the chapter.
Chapter 24
Circulatory Shock and Physiology of Its Treatment
283
15
Cardiac output (L/min)
0 time
2 hours
10
4 hours
41/2 hours
43/4 hours
5
5 hours
0
–4
0
4
8
12
Right atrial pressure (mm Hg)
Figure 24–4
Cardiac output curves of the heart at different times after hemorrhagic shock begins. (These curves are extrapolated to the human
heart from data obtained in dog experiments by Dr. J. W. Crowell.)
Figure 24–5
Generalized Cellular Deterioration. As shock becomes
severe, many signs of generalized cellular deterioration occur throughout the body. One organ especially
affected is the liver, as illustrated in Figure 24–5. This
occurs mainly because of lack of enough nutrients to
support the normally high rate of metabolism in liver
cells, but also partly because of the extreme exposure
of the liver cells to any vascular toxin or other abnormal metabolic factor occurring in shock.
Among the damaging cellular effects that are
known to occur in most body tissues are the following:
1. Active transport of sodium and potassium
through the cell membrane is greatly diminished.
As a result, sodium and chloride accumulate in
the cells, and potassium is lost from the cells. In
addition, the cells begin to swell.
2. Mitochondrial activity in the liver cells, as well as
in many other tissues of the body, becomes
severely depressed.
3. Lysosomes in the cells in widespread tissue areas
begin to break open, with intracellular release of
hydrolases that cause further intracellular
deterioration.
4. Cellular metabolism of nutrients, such as glucose,
eventually becomes greatly depressed in the last
stages of shock. The actions of some hormones
are depressed as well, including almost 100 per
cent depression of the action of insulin.
All these effects contribute to further deterioration
of many organs of the body, including especially (1)
the liver, with depression of its many metabolic and
detoxification functions; (2) the lungs, with eventual
development of pulmonary edema and poor ability to
oxygenate the blood; and (3) the heart, thereby further
depressing its contractility.
Necrosis of the central portion of a liver lobule in severe circulatory shock. (Courtesy Dr. J. W. Crowell.)
Tissue Necrosis in Severe Shock—Patchy Areas of
Necrosis Occur Because of Patchy Blood Flows in
Different Organs. Not all cells of the body are equally
damaged by shock, because some tissues have better
blood supplies than others. For instance, the cells adjacent to the arterial ends of capillaries receive better
nutrition than cells adjacent to the venous ends of the
same capillaries. Therefore, one would expect more
nutritive deficiency around the venous ends of capillaries than elsewhere. This is precisely the effect that
Crowell discovered in studying tissue areas in many
parts of the body. For instance, Figure 24–5 shows
necrosis in the center of a liver lobule, the portion of
the lobule that is last to be exposed to the blood as it
passes through the liver sinusoids.
Similar punctate lesions occur in heart muscle,
although here a definite repetitive pattern, such as
occurs in the liver, cannot be demonstrated. Nevertheless, the cardiac lesions play an important role in
leading to the final irreversible stage of shock. Deteriorative lesions also occur in the kidneys, especially in
the epithelium of the kidney tubules, leading to kidney
failure and occasionally uremic death several days
later. Deterioration of the lungs also often leads to respiratory distress and death several days later—called
the shock lung syndrome.
Acidosis in Shock. Most metabolic derangements that
occur in shocked tissue can lead to blood acidosis all
through the body. This results from poor delivery of
oxygen to the tissues, which greatly diminishes oxidative metabolism of the foodstuffs. When this occurs,
the cells obtain most of their energy by the anaerobic
The Circulation
process of glycolysis, which leads to tremendous quantities of excess lactic acid in the blood. In addition, poor
blood flow through tissues prevents normal removal
of carbon dioxide. The carbon dioxide reacts locally
in the cells with water to form high concentrations of
intracellular carbonic acid; this, in turn, reacts with
various tissue chemicals to form still other intracellular acidic substances. Thus, another deteriorative effect
of shock is both generalized and local tissue acidosis,
leading to further progression of the shock itself.
Positive Feedback Deterioration of Tissues
in Shock and the Vicious Circle of
Progressive Shock
All the factors just discussed that can lead to further
progression of shock are types of positive feedback.
That is, each increase in the degree of shock causes a
further increase in the shock.
However, positive feedback does not necessarily
lead to a vicious circle. Whether a vicious circle develops depends on the intensity of the positive feedback.
In mild degrees of shock, the negative feedback mechanisms of the circulation—sympathetic reflexes,
reverse stress-relaxation mechanism of the blood
reservoirs, absorption of fluid into the blood from the
interstitial spaces, and others—can easily overcome
the positive feedback influences and, therefore, cause
recovery. But in severe degrees of shock, the deteriorative feedback mechanisms become more and more
powerful, leading to such rapid deterioration of the
circulation that all the normal negative feedback
systems of circulatory control acting together cannot
return the cardiac output to normal.
Considering once again the principles of positive
feedback and vicious circle discussed in Chapter 1, one
can readily understand why there is a critical cardiac
output level above which a person in shock recovers
and below which a person enters a vicious circle of circulatory deterioration that proceeds until death.
Irreversible Shock
After shock has progressed to a certain stage, transfusion or any other type of therapy becomes incapable
of saving the person’s life. The person is then said to
be in the irreversible stage of shock. Ironically, even in
this irreversible stage, therapy can, on rare occasions,
return the arterial pressure and even the cardiac
output to normal or near normal for short periods, but
the circulatory system nevertheless continues to deteriorate, and death ensues in another few minutes to
few hours.
Figure 24–6 demonstrates this effect, showing that
transfusion during the irreversible stage can sometimes cause the cardiac output (as well as the arterial
pressure) to return to normal. However, the cardiac
output soon begins to fall again, and subsequent transfusions have less and less effect. By this time, multiple
deteriorative changes have occurred in the muscle
cells of the heart that may not necessarily affect
100
Hemorrhage
Unit IV
Cardiac output
(percentage of normal)
284
75
50
Progressive
stage
Transfusion
25
Irreversible shock
0
0
30
60
90
Minutes
120
150
Figure 24–6
Failure of transfusion to prevent death in irreversible shock.
the heart’s immediate ability to pump blood but, over
a long period, depress heart pumping enough to cause
death. Beyond a certain point, so much tissue damage
has occurred, so many destructive enzymes have been
released into the body fluids, so much acidosis has
developed, and so many other destructive factors are
now in progress that even a normal cardiac output for
a few minutes cannot reverse the continuing deterioration. Therefore, in severe shock, a stage is eventually
reached at which the person will die even though vigorous therapy might still return the cardiac output to
normal for short periods.
Depletion of Cellular High-Energy Phosphate Reserves in
Irreversible Shock. The high-energy phosphate reserves
in the tissues of the body, especially in the liver and
the heart, are greatly diminished in severe degrees of
shock. Essentially all the creatine phosphate has been
degraded, and almost all the adenosine triphosphate
has downgraded to adenosine diphosphate, adenosine
monophosphate, and, eventually, adenosine. Then
much of this adenosine diffuses out of the cells into the
circulating blood and is converted into uric acid, a
substance that cannot re-enter the cells to reconstitute
the adenosine phosphate system. New adenosine can
be synthesized at a rate of only about 2 per cent of
the normal cellular amount an hour, meaning that
once the high-energy phosphate stores of the cells are
depleted, they are difficult to replenish.
Thus, one of the most devastating end results of
deterioration in shock, and the one that is perhaps
most significant for development of the final state of
irreversibility, is this cellular depletion of these highenergy compounds.
Hypovolemic Shock Caused
by Plasma Loss
Loss of plasma from the circulatory system, even
without loss of red blood cells, can sometimes be
severe enough to reduce the total blood volume
Chapter 24
Circulatory Shock and Physiology of Its Treatment
markedly, causing typical hypovolemic shock similar in
almost all details to that caused by hemorrhage. Severe
plasma loss occurs in the following conditions:
1. Intestinal obstruction is often a cause of severely
reduced plasma volume. Distention of the
intestine in intestinal obstruction partly blocks
venous blood flow in the intestinal walls, which
increases intestinal capillary pressure. This in turn
causes fluid to leak from the capillaries into the
intestinal walls and also into the intestinal lumen.
Because the lost fluid has a high protein content,
the result is reduced total blood plasma protein as
well as reduced plasma volume.
2. In almost all patients who have severe burns or
other denuding conditions of the skin, so much
plasma is lost through the denuded skin areas
that the plasma volume becomes markedly
reduced.
The hypovolemic shock that results from plasma
loss has almost the same characteristics as the shock
caused by hemorrhage, except for one additional complicating factor: the blood viscosity increases greatly as
a result of increased red blood cell concentration in
the remaining blood, and this exacerbates the sluggishness of blood flow.
Loss of fluid from all fluid compartments of the
body is called dehydration; this, too, can reduce the
blood volume and cause hypovolemic shock similar to
that resulting from hemorrhage. Some of the causes of
this type of shock are (1) excessive sweating, (2) fluid
loss in severe diarrhea or vomiting, (3) excess loss of
fluid by nephrotic kidneys, (4) inadequate intake of
fluid and electrolytes, or (5) destruction of the adrenal
cortices, with loss of aldosterone secretion and consequent failure of the kidneys to reabsorb sodium,
chloride, and water, which occurs in the absence of
the adrenocortical hormone aldosterone.
Hypovolemic Shock Caused
by Trauma
One of the most common causes of circulatory shock
is trauma to the body. Often the shock results simply
from hemorrhage caused by the trauma, but it can also
occur even without hemorrhage, because extensive
contusion of the body can damage the capillaries
sufficiently to allow excessive loss of plasma into the
tissues. This results in greatly reduced plasma volume,
with resultant hypovolemic shock.
Various attempts have been made to implicate toxic
factors released by the traumatized tissues as one of
the causes of shock after trauma. However, crosstransfusion experiments into normal animals have
failed to show significant toxic elements.
In summary, traumatic shock seems to result
mainly from hypovolemia, although there might also
be a moderate degree of concomitant neurogenic
shock caused by loss of vasomotor tone, as discussed
next.
285
Neurogenic Shock—Increased
Vascular Capacity
Shock occasionally results without any loss of blood
volume. Instead, the vascular capacity increases so
much that even the normal amount of blood becomes
incapable of filling the circulatory system adequately.
One of the major causes of this is sudden loss of vasomotor tone throughout the body, resulting especially in
massive dilation of the veins. The resulting condition
is known as neurogenic shock.
The role of vascular capacity in helping to regulate
circulatory function was discussed in Chapter 15,
where it was pointed out that either an increase in vascular capacity or a decrease in blood volume reduces
the mean systemic filling pressure, which reduces
venous return to the heart. Diminished venous return
caused by vascular dilation is called venous pooling of
blood.
Causes of Neurogenic Shock. Some neurogenic factors
that can cause loss of vasomotor tone include the
following:
1. Deep general anesthesia often depresses the
vasomotor center enough to cause vasomotor
paralysis, with resulting neurogenic shock.
2. Spinal anesthesia, especially when this extends all
the way up the spinal cord, blocks the sympathetic
nervous outflow from the nervous system and can
be a potent cause of neurogenic shock.
3. Brain damage is often a cause of vasomotor
paralysis. Many patients who have had brain
concussion or contusion of the basal regions of
the brain develop profound neurogenic shock.
Also, even though brain ischemia for a few
minutes almost always causes extreme vasomotor
stimulation, prolonged ischemia (lasting longer
than 5 to 10 minutes) can cause the opposite
effect—total inactivation of the vasomotor
neurons in the brain stem, with consequent
development of severe neurogenic shock.
Anaphylactic Shock and
Histamine Shock
Anaphylaxis is an allergic condition in which the
cardiac output and arterial pressure often decrease
drastically. This is discussed in Chapter 34. It results
primarily from an antigen-antibody reaction that takes
place immediately after an antigen to which the person
is sensitive enters the circulation. One of the principal
effects is to cause the basophils in the blood and mast
cells in the pericapillary tissues to release histamine or
a histamine-like substance. The histamine causes (1) an
increase in vascular capacity because of venous dilation, thus causing a marked decrease in venous return;
(2) dilation of the arterioles, resulting in greatly
reduced arterial pressure; and (3) greatly increased
capillary permeability, with rapid loss of fluid and
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Unit IV
The Circulation
protein into the tissue spaces. The net effect is a great
reduction in venous return and sometimes such
serious shock that the person dies within minutes.
Intravenous injection of large amounts of histamine
causes “histamine shock,” which has characteristics
almost identical to those of anaphylactic shock.
Septic Shock
A condition that was formerly known by the popular
name “blood poisoning” is now called septic shock
by most clinicians. This refers to a bacterial infection
widely disseminated to many areas of the body, with
the infection being borne through the blood from one
tissue to another and causing extensive damage. There
are many varieties of septic shock because of the many
types of bacterial infections that can cause it and
because infection in different parts of the body
produces different effects.
Septic shock is extremely important to the clinician,
because other than cardiogenic shock, septic shock is
the most frequent cause of shock-related death in the
modern hospital.
Some of the typical causes of septic shock include
the following:
1. Peritonitis caused by spread of infection from the
uterus and fallopian tubes, sometimes resulting
from instrumental abortion performed under
unsterile conditions.
2. Peritonitis resulting from rupture of the
gastrointestinal system, sometimes caused by
intestinal disease and sometimes by wounds.
3. Generalized bodily infection resulting from
spread of a skin infection such as streptococcal
or staphylococcal infection.
4. Generalized gangrenous infection resulting
specifically from gas gangrene bacilli, spreading
first through peripheral tissues and finally by way
of the blood to the internal organs, especially the
liver.
5. Infection spreading into the blood from the
kidney or urinary tract, often caused by colon
bacilli.
Special Features of Septic Shock. Because of the multiple
types of septic shock, it is difficult to categorize this
condition. Some features often observed are:
1. High fever.
2. Often marked vasodilation throughout the body,
especially in the infected tissues.
3. High cardiac output in perhaps half of patients,
caused by arteriolar dilation in the infected tissues
and by high metabolic rate and vasodilation
elsewhere in the body, resulting from bacterial
toxin stimulation of cellular metabolism and from
high body temperature.
4. Sludging of the blood, caused by red cell
agglutination in response to degenerating tissues.
5. Development of micro–blood clots in widespread
areas of the body, a condition called disseminated
intravascular coagulation. Also, this causes the
blood clotting factors to be used up, so that
hemorrhaging occurs in many tissues, especially in
the gut wall of the intestinal tract.
In early stages of septic shock, the patient usually
does not have signs of circulatory collapse but only
signs of the bacterial infection. As the infection
becomes more severe, the circulatory system usually
becomes involved either because of direct extension
of the infection or secondarily as a result of toxins
from the bacteria, with resultant loss of plasma into the
infected tissues through deteriorating blood capillary
walls. There finally comes a point at which deterioration of the circulation becomes progressive in the same
way that progression occurs in all other types of shock.
The end stages of septic shock are not greatly different from the end stages of hemorrhagic shock, even
though the initiating factors are markedly different in
the two conditions.
Physiology of Treatment
in Shock
Replacement Therapy
Blood and Plasma Transfusion. If a person is in shock
caused by hemorrhage, the best possible therapy is
usually transfusion of whole blood. If the shock is
caused by plasma loss, the best therapy is administration of plasma; when dehydration is the cause, administration of an appropriate electrolyte solution can
correct the shock.
Whole blood is not always available, such as under
battlefield conditions. Plasma can usually substitute
adequately for whole blood because it increases the
blood volume and restores normal hemodynamics.
Plasma cannot restore a normal hematocrit, but the
human body can usually stand a decrease in hematocrit to about half of normal before serious consequences result, if cardiac output is adequate.
Therefore, in emergency conditions, it is reasonable to
use plasma in place of whole blood for treatment of
hemorrhagic or most other types of hypovolemic
shock.
Sometimes plasma is unavailable. In these instances,
various plasma substitutes have been developed that
perform almost exactly the same hemodynamic functions as plasma. One of these is dextran solution.
Dextran Solution as a Plasma Substitute. The principal
requirement of a truly effective plasma substitute is
that it remain in the circulatory system—that is, not
filter through the capillary pores into the tissue spaces.
In addition, the solution must be nontoxic and must
contain appropriate electrolytes to prevent derangement of the body’s extracellular fluid electrolytes on
administration.
To remain in the circulation, the plasma substitute
must contain some substance that has a large enough
molecular size to exert colloid osmotic pressure. One
of the most satisfactory substances developed for this
Chapter 24
Circulatory Shock and Physiology of Its Treatment
purpose is dextran, a large polysaccharide polymer of
glucose. Certain bacteria secrete dextran as a byproduct of their growth, and commercial dextran can
be manufactured using a bacterial culture procedure.
By varying the growth conditions of the bacteria, the
molecular weight of the dextran can be controlled to
the desired value. Dextrans of appropriate molecular
size do not pass through the capillary pores and, therefore, can replace plasma proteins as colloid osmotic
agents.
Few toxic reactions have been observed when using
purified dextran to provide colloid osmotic pressure;
therefore, solutions containing this substance have
proved to be a satisfactory substitute for plasma in
most fluid replacement therapy.
Treatment of Shock with
Sympathomimetic Drugs—Sometimes
Useful, Sometimes Not
287
the tissues, giving the patient oxygen to breathe can be
of benefit in many instances. However, this frequently
is far less beneficial than one might expect, because the
problem in most types of shock is not inadequate oxygenation of the blood by the lungs but inadequate
transport of the blood after it is oxygenated.
Treatment with Glucocorticoids (Adrenal Cortex Hormones That
Control Glucose Metabolism). Glucocorticoids are fre-
quently given to patients in severe shock for several
reasons: (1) experiments have shown empirically that
glucocorticoids frequently increase the strength of the
heart in the late stages of shock; (2) glucocorticoids
stabilize lysosomes in tissue cells and thereby prevent
release of lysosomal enzymes into the cytoplasm of the
cells, thus preventing deterioration from this source;
and (3) glucocorticoids might aid in the metabolism of
glucose by the severely damaged cells.
Circulatory Arrest
A sympathomimetic drug is a drug that mimics sympathetic stimulation. These drugs include norepinephrine, epinephrine, and a large number of long-acting
drugs that have the same effect as epinephrine and
norepinephrine.
In two types of shock, sympathomimetic drugs have
proved to be especially beneficial. The first of these is
neurogenic shock, in which the sympathetic nervous
system is severely depressed. Administering a sympathomimetic drug takes the place of the diminished
sympathetic actions and can often restore full circulatory function.
The second type of shock in which sympathomimetic drugs are valuable is anaphylactic shock, in
which excess histamine plays a prominent role. The
sympathomimetic drugs have a vasoconstrictor effect
that opposes the vasodilating effect of histamine.
Therefore, either norepinephrine or another sympathomimetic drug is often lifesaving.
Sympathomimetic drugs have not proved to be very
valuable in hemorrhagic shock. The reason is that in
this type of shock, the sympathetic nervous system is
almost always maximally activated by the circulatory
reflexes already; so much norepinephrine and epinephrine are already circulating in the blood that sympathomimetic drugs have essentially no additional
beneficial effect.
Other Therapy
Treatment by the Head-Down Position. When the pressure
falls too low in most types of shock, especially in
hemorrhagic and neurogenic shock, placing the patient
with the head at least 12 inches lower than the feet
helps tremendously in promoting venous return,
thereby also increasing cardiac output. This headdown position is the first essential step in the treatment of many types of shock.
Oxygen Therapy. Because the major deleterious effect of
most types of shock is too little delivery of oxygen to
A condition closely allied to circulatory shock is circulatory arrest, in which all blood flow stops. This
occurs frequently on the surgical operating table as a
result of cardiac arrest or ventricular fibrillation.
Ventricular fibrillation can usually be stopped by
strong electroshock of the heart, the basic principles
of which are described in Chapter 13.
Cardiac arrest often results from too little oxygen in
the anesthetic gaseous mixture or from a depressant
effect of the anesthesia itself. A normal cardiac rhythm
can usually be restored by removing the anesthetic and
immediately applying cardiopulmonary resuscitation
procedures, while at the same time supplying the
patient’s lungs with adequate quantities of ventilatory
oxygen.
Effect of Circulatory Arrest
on the Brain
A special problem in circulatory arrest is to prevent
detrimental effects in the brain as a result of the arrest.
In general, more than 5 to 8 minutes of total circulatory arrest can cause at least some degree of permanent brain damage in more than half of patients.
Circulatory arrest for as long as 10 to 15 minutes
almost always permanently destroys significant
amounts of mental power.
For many years, it was taught that this detrimental
effect on the brain was caused by the acute cerebral
hypoxia that occurs during circulatory arrest.
However, experiments have shown that if blood clots
are prevented from occurring in the blood vessels of
the brain, this will also prevent most of the early deterioration of the brain during circulatory arrest. For
instance, in animal experiments performed by Crowell,
all the blood was removed from the animal’s blood
vessels at the beginning of circulatory arrest and
then replaced at the end of circulatory arrest so that
no intravascular blood clotting could occur. In this
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Unit IV
The Circulation
experiment, the brain was usually able to withstand up
to 30 minutes of circulatory arrest without permanent
brain damage.Also, administration of heparin or streptokinase (to prevent blood coagulation) before cardiac
arrest was shown to increase the survivability of the
brain up to two to four times longer than usual.
It is likely that the severe brain damage that occurs
from circulatory arrest is caused mainly by permanent
blockage of many small blood vessels by blood clots,
thus leading to prolonged ischemia and eventual death
of the neurons.
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